Protein adducts as dosimeters of human exposure to styrene, styrene-7,8-oxide, and benzene

Cysteinyl adducts of hemoglobin (Hb) and albumin (Alb) formed via reactions with reactive species were measured in 48 subjects exposed to styrene (0.2 4-55.2 ppm) and to styrene-7,8-oxide (SO) (2.65-107 ppb) in a factory produ cing boats in the USA. Hb and Alb adducts were also investigated among 88 w orkers exposed to benzene (0-138 ppm) in several Chinese factories. The par ticular adducts were S-(2-hydroxy-1-phenylethyl) cysteine, from reactions o f SO with Alb (designated SO-Alb), and S-phenylcysteine, from reactions of the CYP450 benzene metabolite, benzene oxide (BO), with Hb and Alb (designa ted BO-Hb and BO-Alb, respectively). The relationships between adduct level s and exposures were investigated in both studies. The estimated slopes var ied considerably among the particular combinations of adduct and agent to w hich the workers were exposed, ranging from 0.815 pmol BO-Hb/g Hb per ppm b enzene to 24400 pmol SO-Alb/g Alb per ppm SO. We used these estimated slope s, along with kinetic constants, to predict the systemic doses of SO and BO in humans per mg of styrene, SO or benzene per kg body weight, under certa in assumptions. Using RX to signify the particular electrophile (SO or BO) the doses of RX to the blood per unit of dose varied between 2.21 and 4110 nM RX-h/mg agent per kg b.w. The dose of RX to the blood arising from inhal ation of SO was almost 2000 times that of styrene (i.e. 4110 vs. 2.21 nM RX /mg agent per kg b.w.) and 430-781 times that of benzene (i.e. 4110 vs. 5.2 6-9.55 nM RX/mg agent per kg b.w.), depending upon the study. Comparable es timates of the blood dose of BO were obtained from adducts of Hb and Alb an d two independent studies of BO-Alb yielded similar dose estimates. These r esults point to the utility of protein adducts as dosimeters of reactive el ectrophilic species in occupational studies. Finally, significant levels of background adducts of SO and BO with Hb and Alb were observed among worker s, among control subjects and in commercial human proteins. Levels of these background adducts were too great to have arisen from non-occupational exp osures to styrene or benzene or from cigarette smoking. (C) 1999 Elsevier S cience Ireland Ltd. All rights reserved.